title: The activity of several peptide fragments of parathyroid hormone, alone and in combination with salmon calcitonin and morphine, in antinociceptive tests in the mouse.
abstract: Fragments of the parathyroid hormone (PTH) molecule were investigated for intrinsic antinociceptive effects and modulation of salmon calcitonin- and morphine-induced antinociception. Intraventricularly administered PTH 1-34 produced naloxone-insensitive antinociception in both the tail-flick and hot-plate tests. PTH 1-34 antinociceptive effects in the tail-flick test were blocked by i.c.v. salmon calcitonin (sCT, 2 micrograms) and i.c.v. calcium chloride (0.12 mumol). [tyrosine-34]b-PTH (7-34)NH2, the PTH antagonist, did not block PTH 1-34-induced antinociception. PTH 1-34 (2 micrograms) was additive with antinociceptive doses of sCT, but not morphine, in the hot-plate test. PTH 44-68 (0.3 micrograms/mouse, icv.) produced hyperalgesic effects 30 min after administration using the hot-plate test. PTH 44-68 (2 micrograms/mouse) attenuated sCT-induced but not morphine-induced antinociception in both the hot-plate and tail-flick tests. PTH 64-84 was inactive in all tests, alone or in combination with sCT or morphine. Due to the low efficacy of PTH 1-34 and 44-68 in antinociceptive tests, these PTH fragments may act as modulators of antinociception rather than directly producing antinociceptive or hyperalgesic effects. In addition, the results indicate that sCT and the PTH fragments 1-34 and 44-68 may interact in the modulation of nonopiate antinociception, possibly via opposing actions on calcium in the brain.
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Virginia, Richmond.
authors.forename: S P
authors.initials: SP
authors.lastname: Welch
authors.forename: W L
authors.initials: WL
authors.lastname: Dewey
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000139:chemically induced; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D009020:Morphine; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium